Low, non-psychedelic doses of psilocybin as a novel treatment for MASLD, obesity and type 2 diabetes via 5-HT2B receptor-dependent mechanisms
Pharmacological Research December 29, 2025 Martina Colognesi, Daniela Gabbia, Anna Signor et al. 3 citations
Chronic low-dose psilocybin (0.05 mg/kg) reduced body-weight gain, liver steatosis, hyperglycemia, and insulin resistance in mice fed a high-fat/high-fructose diet, without causing central nervous system effects. Multi-omics analyses showed near-complete normalization of disrupted hepatic lipid and carbohydrate metabolism pathways. Psilocybin also improved muscle strength and function, potentially through restoration of leptin sensitivity. The metabolic benefits were independent of the psychedelic target 5-HT2A and instead resulted from antagonism of the serotonin 5-HT2B receptor in the liver, supporting psilocybin as a potential novel therapeutic for metabolic disorders.